The role of resistin-like molecules in natural immune system involving insulin resistance.

• Project/Area Number: 23791047
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: The Institute for Adult Diseases Asahi Life Foundation
• Principal Investigator: KUSHIYAMA Akifumi 公益財団法人朝日生命成人病研究所, その他部局等, 准教授 (30435820)
• Co-Investigator(Kenkyū-buntansha): ASANO Tomoichiro 広島大学, 医歯(薬)学総合研究科, 教授 (70242063) ; SAKODA Hideyuki 東京大学, 医学部附属病院, 特任講師 (50376464) ; KURIHARA Hiroki 東京大学, 医学系研究科, 教授 (20221947)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: インスリン抵抗性 / メタボリックシンドローム / NASH モデル / マクロファージ / 自然免疫 / Relmβ / 分子血管病態

Research Abstract

Resistin-like molecule (RELM) β, secretory protein homologous to resistin, reportedly contributes to local immune response regulation in gut and bronchial epithelial cells. However, we found that activated macrophages also express RELMβ and thus investigated the role of RELMβ in the insulin resistance. In RELMβ KO mice, insulin resistance is ameliorated, and lipid accumulation, inflammation, and fibrosis in liver is ameliorated in NASH model, compared with control mice. Furthermore, ELISA system measuring RELMβ is developed, and now investigating RELMβexpression accompanied with change of dietary habitat.

Research Products

• [Journal Article] Resistin-Like Molecule β Is Abundantly Expressed in Foam Cells and Is Involved in Atherosclerosis Development. (2013)
  • Author(s): Kushiyama A, Sakoda H, Oue N, Okubo M, Nakatsu Y, Ono H, Fukushima T, Kamata H, Nishimura F, Kikuchi T, Fujishiro M, Nishiyama K, Aburatani H, Kushiyama S, Iizuka M, Taki N, Encinas J, Sentani K, Ogonuki N, Ogura A, Kawazu S, Yasui W, Higashi Y, Kurihara H, Katagiri H, Asano T.
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 33 Issue: 8 Pages: 1986-1993
  • DOI: 10.1161/atvbaha.113.301546
  • Peer Reviewed / Open Access
• [Journal Article] Valsartan restores inflammatory response by macrophages in adipose and hepatic tissues of LPS-infused mice (2013)
  • Author(s): Iwashita M, Nakatsu Y, Sakoda H, Fujishiro M, Kushiyama A, Fukushima T, Kumamoto S, Shinjo T, Kamata H, Nishimura F, Asano T
  • Journal Title: Adipocyte Volume: 2(1) Issue: 1 Pages: 28-32
  • DOI: 10.4161/adip.21837
  • Peer Reviewed
• [Journal Article] Integrator complex plays anessential role inadipose differentiation (2013)
  • Author(s): Otani Y, Nakatsu Y, Sakoda H, Fukushima T, Fujishiro M, Kushiyama A, Okubo H, Tsuchiya Y, Ohno H, Takahashi S, Nishimura F, Kamata H, Katagiri H, Asano T.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 434 Issue: 2 Pages: 197-202
  • DOI: 10.1016/j.bbrc.2013.03.029
  • Peer Reviewed
• [Journal Article] Resistin-like molecule β is abundantly expressed in foam cells and is involved in atherosclerosis development (2013)
  • Author(s): Kushiyama A
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: -
  • Peer Reviewed
• [Journal Article] A 20-year trend of increasing obesity in young patients with poorly controlled type 2 diabetes at first diagnosis in urban Japan (2013)
  • Author(s): Kushiyama A
  • Journal Title: J Diabet Invest. Volume: -
  • Peer Reviewed
• [Journal Article] Integrator complex plays an essential role in adipose differentiation. (2013)
  • Author(s): Otani Y
  • Journal Title: Biochem Biophys Res Commun. Volume: -
  • Peer Reviewed
• [Journal Article] Role of Pin1 in the pathogenesis of non-alcoholic steatohepatitis in a rodent model (2012)
  • Author(s): Nakatsu Y, Otani Y, Sakoda H, Zhang J, Guo Y, Okubo H, Kushiyama A, Fujishiro M, Kikuchi T, Fukushima T, Ohno H, Tsuchiya Y, Kamata H, Nagamachi A, Inaba T, Nishimura F, Katagiri H, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 287 Issue: 53 Pages: 44526-44535
  • DOI: 10.1074/jbc.m112.397133
  • Peer Reviewed
• [Journal Article] Xanthine Oxidoreductase Is Involved in Macrophage Foam Cell Formation and atherosclerosis development (2012)
  • Author(s): Kushiyama A, Okubo H, Sakoda H, Kikuchi T, Fujishiro M, Sato H, Kushiyama S, Iwashita M, Nishimura F, Fukushima T, Nakatsu Y, Kamata H, Kawazu S, Higashi Y, Kurihara H, Asano T.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Issue: 2 Pages: 291-298
  • DOI: 10.1161/atvbaha.111.234559
  • Peer Reviewed
• [Journal Article] Preotic neural crest cells contribute to coronary smooth muscle involving endothelin signalling. (2012)
  • Author(s): Yuichiro Arima
  • Journal Title: Nature Communications Volume: 3 Issue: 1 Pages: 1267-1267
  • DOI: 10.1038/ncomms2258
  • Peer Reviewed
• [Journal Article] Valsartan, independently of AT1 receptor or PPARγ, suppresses LPS-induced macrophage activation and improves insulin resistance in cocultured adipocytes. (2012)
  • Author(s): Iwashita M, Sakoda H, Kushiyama A, Fujishiro M, Ohno H, Nakatsu Y, Fukushima T, Kumamoto S, Tsuchiya Y, Kikuchi T, Kurihara H, Akazawa H, Komuro I, Kamata H, Nishimura F, Asano T.
  • Journal Title: American Journal of Physiology - Endocrinology and Metabolism Volume: 302 Issue: 3 Pages: 286-296
  • DOI: 10.1152/ajpendo.00324.2011
  • Peer Reviewed
• [Journal Article] Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with IRS-1 and enhances insulin actions and adipogenesis (2011)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Zhang J, Ono H, Fujishiro M, Kikuchi T, Fukushima T, Yoneda M, Ohno H, Horike N, Kanna M, Tsuchiya Y, Kamata H, Nishimura F, Isobe T, Ogihara T, Katagiri H, Oka Y, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 286 Issue: 23 Pages: 20812-20822
  • DOI: 10.1074/jbc.m110.206904
  • Peer Reviewed
• [Journal Article] Risk of macrovascular disease stratified by stage of chronic kidney disease in type 2 diabetic patients: critical level of the estimated glomerular filtration rate and the significance of hyperuricemia (2011)
  • Author(s): Tanaka K, Hara S, Kushiyama A, Ubara Y, Yoshida Y, Mizuiri S, Aikawa A, Kawatzu S
  • Journal Title: Clin Exp Nephrol Volume: 15(3) Issue: 3 Pages: 391-7
  • DOI: 10.1007/s10157-011-0420-6
  • NAID: 10029005803
  • Peer Reviewed
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity (2011)
  • Author(s): Ohno H, Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Otani Y, Okubo H, Yoneda M, Fukushima T, Kamata H, Nishimura F, Kurihara H, Katagiri H, Oka Y, Asano T
  • Journal Title: Am J Physiol Cell Physiol Volume: 300(5) Issue: 5 Pages: 1047-54
  • DOI: 10.1152/ajpcell.00416.2010
  • Peer Reviewed
• [Journal Article] Adipocyte-macrophage interaction may mediate LPS-induced low-grade inflammation : Potential link with metabolic complications (2011)
  • Author(s): Nakarai, H, Yamashita, A, Nagayasu, S, Iwashita, M, Kumamoto, S, Ohyama, H, Hata, M, Soga, Y, Kushiyama, A, Asano, T, Abiko, Y, Nishimura, F
  • Journal Title: Innate Immunity Volume: 18 Issue: 1 Pages: 164-170
  • DOI: 10.1177/1753425910393370
  • Peer Reviewed
• [Journal Article] Atrio-His (James) accessory pathway and infiltration of γδ T cells in the heart with MELAS (2011)
  • Author(s): Matsuzaki G, Kushiyama A, Uto K, Shoda M, Seko Y
  • Journal Title: BMJ Case Rep Volume: 2011 Issue: jan29 1 Pages: bcr0920103359-bcr0920103359
  • DOI: 10.1136/bcr.09.2010.3359
• [Presentation] インスリン抵抗性および大血管障害におけるマクロファージ由来resistin like molecule βの意義(Research Travel Grant 受賞) (2012)
  • Organizer: 第24回 分子糖尿病研究会
  • Place of Presentation: 東京・品川インターシティー
  • Year and Date: 2012-12-08
• [Presentation] A 20-year trend of patients with type 2 diabetes at first diagnosis in urban Japan (2012)
  • Organizer: 第9回国際糖尿病連合西太平洋地区会議・第4回アジア糖尿病学会学術集会
  • Place of Presentation: 京都・国立京都国際会館
• [Presentation] インスリン分泌能と関連する血糖変動の指標の特徴 (2012)
  • Organizer: 第55回日本糖尿病学会学術総会
  • Place of Presentation: 神奈川・パシフィコ横浜
• [Presentation] インスリン分泌能と関連する 血糖変動指標の特徴 (2012)
  • Author(s): 櫛山暁史
  • Organizer: 第55回日本糖尿病学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Multifunctional Cardiography（MCG）を用いた2型糖尿病患者の心筋虚血の検出 (2012)
  • Author(s): 福井美弥子
  • Organizer: 第55回日本糖尿病学会学術総会
  • Place of Presentation: 横浜
• [Presentation] A 20-year trend of patients with type 2 diabetes at first diagnosis in urban Japan (2012)
  • Author(s): 櫛山暁史
  • Organizer: 2012 IDF-WPR AASD
  • Place of Presentation: 京都
• [Presentation] インスリン抵抗性および大血管障害における マクロファージ由来resistin like molecule βの意義 (2012)
  • Author(s): 櫛山暁史
  • Organizer: 第24回分子糖尿病学シンポジウム
  • Place of Presentation: 東京
• [Presentation] 2型糖尿病患者における骨折リスクに関する横断的研究 (2011)
  • Organizer: 第13回骨粗鬆症学会 健診・骨ドック分科会
  • Place of Presentation: 兵庫・神戸国際会議場
• [Presentation] Mechanism of atherosclerosis development facilitated by resistin like molecule beta (2011)
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都・国立京都国際会館
• [Presentation] 「キサンチンオキシダーゼ経路のマクロファージ泡沫化と動脈硬化への関与」「CGM からみた血糖変動指標と糖尿病の病態の検討」 (2011)
  • Organizer: 第54回日本糖尿病学会学術総会
  • Place of Presentation: 北海道・さっぽろ芸術文化の館他4箇所
• [Presentation] ２型糖尿病患者における骨折リスクに関する横断的研究 (2011)
  • Author(s): 櫛山 暁史
  • Organizer: 第１３回骨粗鬆症学会 健診・骨ドック分科会
  • Place of Presentation: 神戸国際会議場（兵庫県 神戸市）
• [Presentation] Mechanism of atherosclerosis development facilitated by resistin like molecule beta (2011)
  • Author(s): 櫛山 暁史
  • Organizer: 第８４回日本生化学会大会
  • Place of Presentation: 神戸ポートピアホテル(兵庫県 神戸市)
• [Presentation] キサンチンオキシダーゼ経路のマクロファージ泡沫化と動脈硬化への関与（一般口演） (2011)
  • Author(s): 櫛山 暁史
  • Organizer: 第５４回日本糖尿病学会学術総会
  • Place of Presentation: 札幌プリンスホテル（北海道 札幌市）
• [Presentation] CGMからみた血糖変動指標と 糖尿病の病態の検討（一般口演） (2011)
  • Author(s): 金子 由梨
  • Organizer: 第５４回日本糖尿病学会学術総会
  • Place of Presentation: 札幌市教育文化会館（北海道 札幌市）
• [Book] 看護学大辞典 第6版 (2013)
  • Publisher: メヂカルフレンド社
• [Book] 看護学大辞典第6版 (2012)
  • Author(s): 永井良三
  • Total Pages: 2400
  • Publisher: メヂカルフレンド社
• [Remarks]
  • URL: http://www.asahi-life.or.jp/laboratory/biomolecular.html
• [Remarks] 朝日生命成人病研究所 研究部 糖尿病代謝科 分子生物学班
  • URL: http://www.asahi-life.or.jp/laboratory/biomolecular.html
• [Remarks]
  • URL: http://www.asahi-life.or.jp/laboratory/biomolecular.html
• [Patent(Industrial Property Rights)] 大腸癌、動脈硬化症、又はメタボリックシンドロームの検出方法 (2013)
  • Inventor(s): 浅野 知一郎、櫛山 暁史
  • Industrial Property Rights Holder: 広島大学・朝日生命成人病研究所
  • Acquisition Date: 2013-03-29
• [Patent(Industrial Property Rights)] 大腸癌、動脈硬化症又はメタボリックシンドロームの検出法 (2013)
  • Inventor(s): 櫛山暁史
  • Industrial Property Rights Holder: 櫛山暁史
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-02-28
• [Patent(Industrial Property Rights)] 大腸癌、動脈硬化症、又はメタボリックシンドロームの検出方法 (2012)
  • Inventor(s): 浅野 知一郎、櫛山 暁史
  • Industrial Property Rights Holder: 広島大学・朝日生命成人病研究所
  • Industrial Property Number: 2013-040964
  • Filing Date: 2012-11-26